Regulatory Mechanisms of Intrinsic Activity in Detrusor Smooth Muscle

Description of projects available to graduate students:
Normal healthy bladder smooth muscle (detrusor) displays random, isolated regions of contractile activity across the surface of the bladder during the filling phase. This mechanism is hypothesized to allow for low intravesical pressure as the bladder fills with urine.

However, in pathologies such as partial bladder outlet obstruction or spinal cord injury, this activity is significantly altered and is thought to be one of the underlying causes of detrusor overactivity. The amplitude of the contractions is significantly increased. In some cases the magnitude is near that seen with micturition contractions and may contribute to urinary incontinence.

Our project focuses on the mechanisms by which intrinsic detrusor contractions are modulated, specifically by bladder interstitial cells. It is believed that as the bladder fills there are signaling factors (e.g. ATP, nitric oxide, prostaglandins, acetylcholine) released in response to distention from the epithelial (urothelium) lining of the lumen. These factors, in turn, activate interstitial cells in the suburothelium that connect to a network of interstitial cells throughout the bladder to regulate smooth muscle contractility.

The overall aim of the project is to determine how interstitial cell communicate to the urothelium, sensory nerves, smooth muscle and other interstitial cells. It is believed that this unique intrinsic communication network may present a target for new therapeutics in the treatment of detrusor overactivity.

The project involves a range of techniques including; in vivo cystometric measurements, optical mapping of Ca2+ and membrane voltage changes from isolated tissue preparations, electrophysiological nerve recordings, immunohistochemistry, and epifluorescence studies from cultured cells.

Techniques graduate student will learn:
See above.